Paulo Alexandre de Oliveira, Ph.D.

@article{Remor:2018aa,

title = {Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation.},

author = {Aline Pertile Remor and Rodrigo Augusto da Silva and Filipe Jose de Matos and Viviane Glaser and Roberta de Paula Martins and Karina Ghisoni and Debora da Luz Scheffer and Denise Carleto Andia and Daniele Portinho and Ana Paula de Souza and Paulo Alexandre de Oliveira and Rui Daniel Prediger and Alicia I Torres and Rose Marie Mueller Linhares and Roger Walz and Marcelo Fernando Ronsoni and Alexandre Hohl and Alex Rafacho and Aderbal Silva Jr Aguiar and Ana Lucia De Paul and Alexandra Latini},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29948953},

doi = {10.1007/s12035-018-1175-9},

issn = {1559-1182 (Electronic); 0893-7648 (Linking)},

year  = {2018},

date = {2018-06-14},

journal = {Mol Neurobiol},

address = {Laboratorio de Bioenergetica e Estresse Oxidativo (LABOX), Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina (UFSC), Campus Universitario - Corrego Grande, Bloco C 201/214, Florianopolis, SC, 88040-900, Brazil.},

abstract = {Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromised cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in rats. The mechanisms appear to be linked to reduced active DNA demethylation and diminished expression of the neuroprotective transcription factor REST. The impact of the relationship between adiposity and DNA hypermethylation on REST expression was also demonstrated in peripheral blood mononuclear cells in obese children with reduced levels of blood ascorbate. The reversible nature of epigenetic modifications and the cognitive impairment reported in obese children, adolescents, and adults suggest that the correction of the anthropometry and the peripheral metabolic alterations would protect brain homeostasis and reduce the risk of developing neurodegenerative diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Latini:2018aa,

title = {Tetrahydrobiopterin improves hippocampal nitric oxide-linked long-term memory.},

author = {Alexandra Latini and Lucila de Bortoli da Silva and Debora da Luz Scheffer and Ananda Christina Staats Pires and Filipe Jose de Matos and Renata T Nesi and Karina Ghisoni and Roberta de Paula Martins and Paulo Alexandre de Oliveira and Rui D Prediger and Marisa Ghersi and Laura Gabach and Mariela Fernanda Perez and Susana Rubiales-Barioglio and Rita Raisman-Vozari and Raymond Mongeau and Laurence Lanfumey and Aderbal Silva Aguiar},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29935801},

doi = {10.1016/j.ymgme.2018.06.003},

issn = {1096-7206 (Electronic); 1096-7192 (Linking)},

year  = {2018},

date = {2018-06-11},

journal = {Mol Genet Metab},

address = {Laboratorio de Bioenergetica e Estresse Oxidativo - LABOX, Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil. Electronic address: alexandra.latini@childrens.harvard.edu.},

abstract = {Tetrahydrobiopterin (BH4) is synthesized by the combined action of three metabolic pathways, namely de novo synthesis, recycling, and salvage pathways. The best-known function of BH4 is its mandatory action as a natural cofactor of the aromatic amino acid hydroxylases and nitric oxide synthases. Thus, BH4 is essential for the synthesis of nitric oxide, a retrograde neurotransmitter involved in learning and memory. We investigated the effect of BH4 (4-4000pmol) intracerebroventricular administration on aversive memory, and on BH4 metabolism in the hippocampus of rodents. Memory-related behaviors were assessed in Swiss and C57BL/6J mice, and in Wistar rats. It was consistently observed across all rodent species that BH4 facilitates aversive memory acquisition and consolidation by increasing the latency to step-down in the inhibitory avoidance task. This effect was associated with a reduced threshold to generate hippocampal long-term potentiation process. In addition, two inhibitors of memory formation (N(omega)-nitro-L-arginine methyl ester - L-Name - and dizocilpine - MK-801 -) blocked the enhanced effect of BH4 on memory, while the amnesic effect was not rescue by the co-administration of BH4 or a cGMP analog (8-Br-cGMP). The data strongly suggest that BH4 enhances aversive memory by activating the glutamatergic neurotransmission and the retrograde activity of NO. It was also demonstrated that BH2 can be converted into BH4 by activating the BH4 salvage pathway under physiological conditions in the hippocampus. This is the first evidence showing that BH4 enhances aversive memory and that the BH4 salvage pathway is active in the hippocampus.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cattani:2017aa,

title = {Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: Implication of glutamate excitotoxicity and oxidative stress.},

author = {Daiane Cattani and Patricia Acordi Cesconetto and Mauren Kruger Tavares and Eduardo Benedetti Parisotto and Paulo Alexandre De Oliveira and Carla Elise Heinz Rieg and Marina Concli Leite and Rui Daniel Schroder Prediger and Nestor Cubas Wendt and Guilherme Razzera and Danilo Wilhelm Filho and Ariane Zamoner},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28627408},

doi = {10.1016/j.tox.2017.06.001},

issn = {1879-3185 (Electronic); 0300-483X (Linking)},

year  = {2017},

date = {2017-07-15},

journal = {Toxicology},

volume = {387},

pages = {67--80},

address = {Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brazil; Programa de Pos-Graduacao em Farmacia, Centro de Ciencias da Saude, Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brazil.},

abstract = {We have previously demonstrated that maternal exposure to glyphosate-based herbicide (GBH) leads to glutamate excitotoxicity in 15-day-old rat hippocampus. The present study was conducted in order to investigate the effects of subchronic exposure to GBH on some neurochemical and behavioral parameters in immature and adult offspring. Rats were exposed to 1% GBH in drinking water (corresponding to 0.36% of glyphosate) from gestational day 5 until postnatal day (PND)-15 or PND60. Results showed that GBH exposure during both prenatal and postnatal periods causes oxidative stress, affects cholinergic and glutamatergic neurotransmission in offspring hippocampus from immature and adult rats. The subchronic exposure to the pesticide decreased L-[(14)C]-glutamate uptake and increased (45)Ca(2+) influx in 60-day-old rat hippocampus, suggesting a persistent glutamate excitotoxicity from developmental period (PND15) to adulthood (PND60). Moreover, GBH exposure alters the serum levels of the astrocytic protein S100B. The effects of GBH exposure were associated with oxidative stress and depressive-like behavior in offspring on PND60, as demonstrated by the prolonged immobility time and decreased time of climbing observed in forced swimming test. The mechanisms underlying the GBH-induced neurotoxicity involve the NMDA receptor activation, impairment of cholinergic transmission, astrocyte dysfunction, ERK1/2 overactivation, decreased p65 NF-kappaB phosphorylation, which are associated with oxidative stress and glutamate excitotoxicity. These neurochemical events may contribute, at least in part, to the depressive-like behavior observed in adult offspring.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Oliveira:2017aa,

title = {Moderate traumatic brain injury increases the vulnerability to neurotoxicity induced by systemic administration of 6-hydroxydopamine in mice.},

author = {Paulo Alexandre de Oliveira and Juliana Ben and Filipe Carvalho Matheus and Marcelo Liborio Schwarzbold and Eduardo Luiz Gasnhar Moreira and Daniel Rial and Roger Walz and Rui Daniel Prediger},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28288867},

doi = {10.1016/j.brainres.2017.03.002},

issn = {1872-6240 (Electronic); 0006-8993 (Linking)},

year  = {2017},

date = {2017-05-15},

journal = {Brain Res},

volume = {1663},

pages = {78--86},

address = {Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianopolis 88049-900, Brazil.},

abstract = {Moderate traumatic brain injury (TBI) might increase the vulnerability to neuronal neurodegeneration, but the basis of such selective neuronal susceptibility has remained elusive. In keeping with the disruption of the blood-brain barrier (BBB) caused by TBI, changes in BBB permeability following brain injury could facilitate the access of xenobiotics into the brain. To test this hypothesis, here we evaluated whether TBI would increase the susceptibility of nigrostriatal dopaminergic fibers to the systemic administration of 6-hydroxydopamine (6-OHDA), a classic neurotoxin used to trigger a PD-like phenotype in mice, but that in normal conditions is unable to cross the BBB. Adult Swiss mice were submitted to a moderate TBI using a free weight-drop device and, 5h later, they were injected intraperitoneally with a single dose of 6-OHDA (100mg/kg). Afterwards, during a period of 4weeks, the mice were submitted to a battery of behavioral tests, including the neurological severity score (NSS), the open field and the rotarod. Animals from the TBI plus 6-OHDA group displayed significant motor and neurological impairments that were improved by acute l-DOPA administration (25mg/kg, i.p.). Moreover, the observation of the motor deficits correlates with (i) a significant decrease in the tyrosine hydroxylase levels mainly in the rostral striatum and (ii) a significant increase in the levels of striatal glial fibrillary acidic protein (GFAP) levels. On the whole, the present findings demonstrate that a previous moderate TBI event increases the susceptibility to motor, neurological and neurochemical alterations induced by systemic administration of the dopaminergic neurotoxin 6-OHDA in mice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Oliveira:2017ab,

title = {Angiotensin II type 1/adenosine A 2A receptor oligomers: a novel target for tardive dyskinesia.},

author = {Paulo A de Oliveira and James A R Dalton and Marc Lopez-Cano and Adria Ricarte and Xavier Morato and Filipe C Matheus and Andreia S Cunha and Christa E Muller and Reinaldo N Takahashi and Victor Fernandez-Duenas and Jesus Giraldo and Rui D Prediger and Francisco Ciruela},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28500295},

doi = {10.1038/s41598-017-02037-z},

issn = {2045-2322 (Electronic); 2045-2322 (Linking)},

year  = {2017},

date = {2017-05-12},

journal = {Sci Rep},

volume = {7},

number = {1},

pages = {1857},

address = {Departamento de Farmacologia, Universidade Federal de Santa Catarina, Trindade, 88049-900, Florianopolis, SC, Brazil.},

abstract = {Tardive dyskinesia (TD) is a serious motor side effect that may appear after long-term treatment with neuroleptics and mostly mediated by dopamine D2 receptors (D2Rs). Striatal D2R functioning may be finely regulated by either adenosine A2A receptor (A2AR) or angiotensin receptor type 1 (AT1R) through putative receptor heteromers. Here, we examined whether A2AR and AT1R may oligomerize in the striatum to synergistically modulate dopaminergic transmission. First, by using bioluminescence resonance energy transfer, we demonstrated a physical AT1R-A2AR interaction in cultured cells. Interestingly, by protein-protein docking and molecular dynamics simulations, we described that a stable heterotetrameric interaction may exist between AT1R and A2AR bound to antagonists (i.e. losartan and istradefylline, respectively). Accordingly, we subsequently ascertained the existence of AT1R/A2AR heteromers in the striatum by proximity ligation in situ assay. Finally, we took advantage of a TD animal model, namely the reserpine-induced vacuous chewing movement (VCM), to evaluate a novel multimodal pharmacological TD treatment approach based on targeting the AT1R/A2AR complex. Thus, reserpinized mice were co-treated with sub-effective losartan and istradefylline doses, which prompted a synergistic reduction in VCM. Overall, our results demonstrated the existence of striatal AT1R/A2AR oligomers with potential usefulness for the therapeutic management of TD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}